Myocardial Protection by Vagal Stimulation in Ischemia-Reperfusion Injury in Mice

Abstract

Background: The beneficial effects of prolonged vagal stimulation (VS) applied during myocardial infarction have been previously demonstrated. However, the effects and mechanisms of protection are unknown when VS is applied selectively and briefly before ischemia or at the onset of reperfusion. Objective: The aim of this study was to analyze whether VS applied during reperfusion is capable of reducing infarct size similarly to preischemic VS, and whether in both cases muscarinic or nicotinic receptors mediate the protection. Methods: FVB mice were subjected to 30 minutes of regional myocardial ischemia and 2-hour reperfusion without VS (I/R); with 10 minutes preischemic VS (pVS), with pVS and muscarinic blockade by atropine and with pVS and α-7 nicotinic blockade by methyllycaconitine. The effects of VS at the onset of reperfusion (rVS) were also studied with atropine and with methyllycaconitine. A left ventricular catheter was used to measure ventricular function. Area at risk was measured using Evans blue and infarct size was assessed with 2,3,5-triphenyltetrazolium. Results: Vagal stimulation during reperfusion reduced infarct size similarly to pVS, albeit with different mechanisms of protection. Preischemic VS protected the heart through cholinergic activation of muscarinic receptors, while rVS protection was effected through an α-7 cholinergic nicotinic pathway. Conclusion: The present study demonstrated for the first time in an ischemia-reperfusion mice model that a brief 10-minute period of VS is able to similarly reduce infarct size when it is applied prior to ischemia or at the onset of reperfusion, mimicking ischemic preconditioning and postconditioning, respectively.